Takaisin

Glaukoomaan liittyvien rakenne- ja näkökenttämuutosten diagnostiikka

Näytönastekatsaukset
Anja Tuulonen ja Ville Saarela
3.7.2014

Näytön aste: D

Satunnaistettuja diagnostisia tutkimuksia siitä, minkä testien käyttö seulonnassa, diagnostiikassa ja seurannassa vähentää glaukooman aiheuttamaa näkövammaisuutta ja olisi kustannusvaikuttavaa, ei ole julkaistu. Diagnostisten testien arviointia vaikeuttaa kultaisen standardin puuttuminen ja julkaistujen tutkimusten suuri harhan riski.

Systemaattinen katsaus 1

Highly sensitive systematic electronic searches for this systematic review «Burr JM, Mowatt G, Hernández R ym. The clinical ef...»1 were undertaken by December 2005. The diagnostic accuracy review of diagnostics and screening tests included 40 studies totaling more than 48 000 participants ≥ 40 years. The primary reference standard was confirmation of OAG at follow-up examination. Also considered was diagnosis of OAG requiring treatment. No studies were at low risk of bias. A small subset of eight studies was judged to have higher quality. Most potential screening tests reviewed had an estimated specificity of 85 % or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Systemaattinen katsaus 2

A systematic review «Ervin AE, Boland MV, Myrowitz EH ym. Screening for...»2 through October 6, 2011 was conducted from MEDLINE®, Embase, LILACS, and CENTRAL through October 6, 2011, and MEDLINE and CENTRAL (March 2, 2011) and screening of an existing database to identify relevant systematic reviews.

After the Burr et al. 2007 systematic review «Burr JM, Mowatt G, Hernández R ym. The clinical ef...»1, 4,960 studies were identified, of which 83 studies addressing the accuracy of screening and diagnostic tests were eligible. The sensitivity of standard automated perimetry (SAP) was higher than Goldmann tonometry, similar to the Heidelberg retina tomograph (HRT), and lower than disc photos or frequency doubling technology (FDT) visual field testing. The specificity of SAP was higher than disc photos and FDT, similar to HRT, and lower than Goldmann tonometry. Some comparisons of tests could not be performed due to variability in populations and reported thresholds. No other studies were identified.

68 % of studies were at high risk of spectrum bias (not representative of those who would receive the test in practice). 6 % had differential verification bias (different reference standards). The candidate tests were interpreted without knowledge of reference standard in only 29 % of studies. 48 % of the studies did not include an explanation of withdrawals from the study, and 46 % of the studies reported the number of uninterpretable test results. Only 3 of 83 studies included a population-based sample.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Systemaattinen katsaus 3

A systematic search for this systematic review «Tarride JE, Burke N, Hopkins RB ym. New glaucoma d...»3 was conducted up to April 2010 to identify studies evaluating 5 new technologies (confocal scanning laser opthalmoscopy by Heidelberg Retina Tomography, optical coherence tomography [OCT], scanning laser polarimetry using GDx-VCC, frequency doubling technology, and blue-on-yellow automated perimetry). The reference standards were optic disc assessment or standard achromaticwhite-on-white perimetry. The review included cost analyses or full economic evaluation studies comparing both costs and consequences associated with these technologies.

Of the 410 unique citations retrieved by the search, 6 articles either presented a cost analysis of tests for glaucoma diagnosis or included a review of published economic studies (Supplementary fig. 1, http://pubs.nrc-cnrc.gc.ca/cjo/cjo.html). Of those, 3 studies presented a cost analysis of scanning lasers and OCT, mostly in terms of costs associated with the diagnostic equipment. However, differences in settings or methods made comparisons between these 3 studies difficult. One study indicated that time required to conduct the test may be an important element to consider in economic evaluations. Other reviews of economic studies of glaucoma screening identified in the search did not cite any published studies evaluating these new technologies.

Despite our extensive search, and in line with previous findings, no cost-effectiveness studies of the newer diagnostic tests could be identified.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

Katsaus 4

A non-systematic review of the literature «Tuulonen A. Economic considerations of the diagnos...»4 was conducted in PubMed by October 2010 with key words Glaucoma and cost*. No randomized screening, diagnostic and follow-up trials were found of the clinical effectiveness nor cost-effectiveness of the optimum test set preventing visual disability

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentti: Kaikissa silmän rakennetta ja toimintaa mittaavissa tutkimuksissa oli menetelmästä (sekä käytetystä strategiasta ja kriteereistä), tutkittavasta ja taudin vaikeusasteesta johtuvaa vaihtelua.

Glaukoomadiagnoosista ei ole tieteellisessä kirjallisuudessa olemassa yleisesti käytettyä ja hyväksyttyä määritelmää «Bathija R, Gupta N, Zangwill L ym. Changing defini...»5. Kun tutkittiin kolmessa johtavassa amerikkalaisjulkaisussa 1980–95 ilmestyneen 182 glaukoomaa käsittelevän artikkelin otosta, niistä vain 2/3-osassa oli esitetty jonkinlainen glaukoomadiagnoosin määritelmä, ja sekin vaihteli huomattavasti artikkelista toiseen.

Jos glaukoomadiagnoosi määritellään nykyisin käytössä olevien näkökentän tutkimusmenetelmien avulla, yhden poikkeavan näkökentän testituloksen merkitys on vähäinen, ja puutoksen varmentaminen vaatii 1–2 lisäkenttää «Schulzer M. Errors in the diagnosis of visual fiel...»6, «The Glaucoma Laser Trial (GLT): 6. Treatment group...»7. Kun seurannassa etenemä varmistettiin 1–2 lisäkentän avulla, 48–86 %:ssa tapauksista kyseessä oli väärä positiivinen löydös «Schulzer M. Errors in the diagnosis of visual fiel...»6, «The Glaucoma Laser Trial (GLT): 6. Treatment group...»7, «Keltner JL, Johnson CA, Quigg JM ym. Confirmation ...»8. Epäluotettavuutta lisää, jos lähtötaso määritellään vain yhden näkökentän perusteella «The Glaucoma Laser Trial (GLT): 6. Treatment group...»7, «Kass MA, Gordon MO. Intraocular pressure and visua...»9.

Rakennevauriot papillassa ja hermosäiekerroksessa edeltävät näkökenttäpuutoksia «Quigley HA, Enger C, Katz J ym. Risk factors for t...»10, «Paczka JA, Friedman DS, Quigley HA ym. Diagnostic ...»11, «Jonas JB, Gründler AE. Correlation between mean vi...»12. Useimmat tautitapaukset – mukaan lukien preperimetrinen glaukooma (näkökenttä on normaali, vaikka silmässä on rakennevauriota) – voidaan diagnosoida, kun tutkitaan näkökentän lisäksi myös papilla- ja hermosäiekerros.

Simulatiomallejamalleja ja retrospektiivisä tutkimuksia

The UK Health Technology Assessment compared five alternative surveillance and treatment pathways in OHT «Burr JM, Botello-Pinzon P, Takwoingi Y ym. Surveil...»13.

  • The two most intensive pathways were based on the NICE guidelines (check-ups from every 4-12 -month to 6-24 -month intervals depending on initial risk), two further pathways followed biennial follow-up schemes differing in location (surveillance either in hospital or in primary care), and in the fifth ‘Treat all’ pathway, all IOPs > 21 mmHg were treated with prostaglandins. In ‘Treat all’ pathway, IOP was measured annually in community optometry with referral to a hospital only if IOP reduction was < 15 %.
  • The results of the model indicated no clear benefit from intensive monitoring in OHT.‘Treat all’ was the least and ‘NICE intensive’ was the most costly pathway.
  • Compared to 'Treat all' –strategy, however, the pathway with 2-year check ups in an eye hospital (and treatment with > 5 % glaucoma risk in 5 years) reduced the incidence of conversion to glaucoma and provided more QALYs. However, simultaneously this pathway cost considerably more - above the limit of the society’s willingness to pay in the UK.
  • For the cost-benefit analysis the biennial hospital pathway was the only pathway relative to ‘no surveillance’ that had a positive net benefit.
  • Tutkimuksen laatu: heikko
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

An economic simulation model in Holland (built on systematic evaluation of literature) «van Gestel A. Glaucoma management. Economic evalua...»14.

  • The results suggested that treating all OHT patients with IOP > 21 mmHg would be cost saving compared to watchful waiting – even if 43 % of the simulated untreated OHT patients never converted to glaucoma in their entire lifetime.
  • In eyes with manifest glaucoma, in lieu of 'guessing' the initial target pressure and redefining it according to rate of progression, the model suggested to aim at a standard IOP < 15 mmHg in all glaucoma patients - even if it the model indicated that 72% would need direct combination therapy and 46 % would require glaucoma surgery. According to the model, these simplified strategies would decrease demand for intensive monitoring.
  • Non-adherence to the medication was not considered in the model. It was assumed that including adherence would have a small impact of the outcomes but would have unnecessarily increased the complexity of the model.
  • Tutkimuksen laatu: heikko
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

The cost data of glaucoma patients were retrospectively collected and compared in two cities in Finland during 11 years «Hagman J. Comparison of resource utilization in th...»15. The patients were examined at the end of follow-up period. In addition, general health related quality of life questionnaire was evaluated.

  • The intensive monitoring frequency, treatment and spending did not lead to better quality of life in glaucoma patients, i.e. 28 % higher medication costs, 46 % higher diagnostic testing and follow-up costs, 3 times more laser therapies and twice more surgery between the two cities.
  • There was actually a statistically significant counter-intuitive difference in the early glaucoma group, i.e. patients using more resources reported worse quality of life.
  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

The report «Crabb DP, Garway-Heath DF. Intervals between visua...»16 aims to determine if identification of progression would be improved by clustering tests at the beginning and end of the 2-year period. Published recommendations suggest that three visual field tests per year are required to identify rapid progression in a newly diagnosed glaucomatous patient over 2 years.

Computer-simulated "patients" were given a rapid VF (mean deviation [MD]) loss of -2 dB/year with added MD measurement variability. Linear regression of MD against time was used to estimate progression. One group of "patients" was measured every 6 months, another every 4 months, whereas the wait-and-see group were measured either 2 or 3 times at both baseline and at the end of a 2-year period. Stable "patients" (0 dB/year) were generated to examine the effect of the follow-up patterns on false-positive (FP) progression identification.

By 2 years, 58% and 82% of rapidly progressing patients were correctly detected using evenly spaced 6- and 4-month VFs, respectively. This power of detection significantly improved to 62% and 95% with the wait-and-see approach (P < 0.001). When compared with evenly spaced VFs, the rate of MD loss was better estimated by the wait-and-see approach, but average detection time was slightly slower. Evenly spaced testing incurred a significantly higher FP rate: up to 5.9% compared with only 0.4% in wait-and-see (P < 0.001).

Authors’ conclusions: Compared with an evenly spaced follow-up, wait-and-see identifies more "patients" with rapid VF progression with fewer FPs, making it particularly applicable to clinical trials.

  • Tutkimuksen laatu: heikko
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

Kirjallisuutta

  1. Burr JM, Mowatt G, Hernández R ym. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation. Health Technol Assess 2007;11:iii-iv, ix-x, 1-190 «PMID: 17927922»PubMed
  2. Ervin AE, Boland MV, Myrowitz EH ym. Screening for Glaucoma: Comparative Effectiveness. Comparative Effectiveness Review Number 59 AHRQ Publication No. 12-EHC037-EF, April 2012; «http://www.effectivehealthcare.ahrq.gov/ehc/products/182/1026/CER59_Glaucoma-Screening_Final-Report_20120524.pdf»1
  3. Tarride JE, Burke N, Hopkins RB ym. New glaucoma diagnostic technologies: a systematic review of economic studies. Can J Ophthalmol 2011;46:89-90 «PMID: 21283168»PubMed
  4. Tuulonen A. Economic considerations of the diagnosis and management for glaucoma in the developed world. Curr Opin Ophthalmol 2011;22:102-9 «PMID: 21192264»PubMed
  5. Bathija R, Gupta N, Zangwill L ym. Changing definition of glaucoma. J Glaucoma 1998;7:165-9 «PMID: 9627855»PubMed
  6. Schulzer M. Errors in the diagnosis of visual field progression in normal-tension glaucoma. Ophthalmology 1994;101:1589-94; discussion 1595 «PMID: 8090461»PubMed
  7. The Glaucoma Laser Trial (GLT): 6. Treatment group differences in visual field changes. Glaucoma Laser Trial Research Group. Am J Ophthalmol 1995;120:10-22 «PMID: 7611312»PubMed
  8. Keltner JL, Johnson CA, Quigg JM ym. Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Ocular Hypertension Treatment Study Group. Arch Ophthalmol 2000;118:1187-94 «PMID: 10980763»PubMed
  9. Kass MA, Gordon MO. Intraocular pressure and visual field progression in open-angle glaucoma. Am J Ophthalmol 2000;130:490-1 «PMID: 11024422»PubMed
  10. Quigley HA, Enger C, Katz J ym. Risk factors for the development of glaucomatous visual field loss in ocular hypertension. Arch Ophthalmol 1994;112:644-9 «PMID: 8185522»PubMed
  11. Paczka JA, Friedman DS, Quigley HA ym. Diagnostic capabilities of frequency-doubling technology, scanning laser polarimetry, and nerve fiber layer photographs to distinguish glaucomatous damage. Am J Ophthalmol 2001;131:188-97 «PMID: 11228294»PubMed
  12. Jonas JB, Gründler AE. Correlation between mean visual field loss and morphometric optic disk variables in the open-angle glaucomas. Am J Ophthalmol 1997;124:488-97 «PMID: 9323939»PubMed
  13. Burr JM, Botello-Pinzon P, Takwoingi Y ym. Surveillance for ocular hypertension: an evidence synthesis and economic evaluation. Health Technol Assess 2012;16:1-271, iii-iv «PMID: 22687263»PubMed
  14. van Gestel A. Glaucoma management. Economic evaluations based on a patient level simulation model. Ipskamp Drukkers, Enschede, Holland, 2012. ISBN 978-94-6191-403-3
  15. Hagman J. Comparison of resource utilization in the treatment of open-angle glaucoma between two cities in Finland: is more better? Acta Ophthalmol 2013;91 Thesis 3:1-47 «PMID: 23621767»PubMed
  16. Crabb DP, Garway-Heath DF. Intervals between visual field tests when monitoring the glaucomatous patient: wait-and-see approach. Invest Ophthalmol Vis Sci 2012;53:2770-6 «PMID: 22427597»PubMed